Greater than one third of all HIV infections and AIDS cases are related directly or indirectly to injection drug use [1, 2]. While it is clear that drug use itself plays an important role in the spread of HIV infection, the effects of the drugs on HIV disease progression are not fully understood and various epidemiologic, animal and in vitro studies have provided some conflicting results. In view of the confounding variables in human epidemiologic studies and problems in previous animal studies investigating this issue, additional studies are needed to determine the role of opioids in contributing to the pathogenesis of HIV infection and the development of AIDS associated CMS disorders. The Specific Aim of this core is to carry out Experimental Animal Protocols in Indian rhesus macaques, to perform certain clinical, virologic, and immunologic measurements and to provide a mechanism of distribution of samples from the ongoing animal protocols to projects and Core D (Immunohistochemical Core) for further analysis. The Core will provide housing, care, scheduled drug treatment interventions, sample collections, clinical and virologic data collection for two sequential protocols to determine the effects of opioids on the pathogenesis of SIV infection and the development of CMS disease. The activities of this core are essential to the overall performance of this Program Project especially since Project 1,2,3, and 4 rely heavily on the samples from rhesus macaques in various treatment groups as well as on clinical and virologic data generated in this core. The proposed studies that this Core will support are critical for our understanding of how opioid drug abuse affects the course of HIV disease progression.. The experimental design of the Experimental Animal Protocol should lead to definitive answers regarding the role of opiates drugs of abuse in altering the pathogenesis of HIV/SIV and in contributing to CMS disease. These studies supported by this Core should provide important insights regarding pathogenesis and therapeutic approaches in patients with HIV infection, particularly those who are opiate drug abusers.